rs2232784

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016579.4(CD320):c.483C>T(p.Ser161Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,602,380 control chromosomes in the GnomAD database, including 4,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2042 hom., cov: 33)

Exomes 𝑓: 0.043 ( 2763 hom. )

Consequence

CD320
NM_016579.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.953

Publications

12 publications found

Variant links:

Genes affected

CD320 (HGNC:16692): (CD320 molecule) This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

CD320 Gene-Disease associations (from GenCC):

methylmalonic acidemia due to transcobalamin receptor defect
Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen, Laboratory for Molecular Medicine

CD320 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-8303874-G-A is Benign according to our data. Variant chr19-8303874-G-A is described in ClinVar as Benign. ClinVar VariationId is 136681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.953 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD320	NM_016579.4 link	c.483C>T	p.Ser161Ser	synonymous_variant	Exon 3 of 5	ENST00000301458.10	NP_057663.1	Q9NPF0-1
CD320	NM_001165895.2 link	c.357C>T	p.Ser119Ser	synonymous_variant	Exon 2 of 4		NP_001159367.1	Q9NPF0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10 link	c.483C>T	p.Ser161Ser	synonymous_variant	Exon 3 of 5	1	NM_016579.4	ENSP00000301458.4		Q9NPF0-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17408

AN:

152184

Hom.:

2034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0688

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.0880

Gnomad SAS

AF:

0.0395

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0347

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.0568

AC:

13061

AN:

229976

AF XY:

0.0515

show subpopulations

Gnomad AFR exome

AF:

0.304

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.0633

Gnomad EAS exome

AF:

0.0868

Gnomad FIN exome

AF:

0.0263

Gnomad NFE exome

AF:

0.0340

Gnomad OTH exome

AF:

0.0467

GnomAD4 exome

AF:

0.0435

AC:

63056

AN:

1450078

Hom.:

2763

Cov.:

AF XY:

0.0423

AC XY:

30457

AN XY:

720494

show subpopulations

African (AFR)

AF:

0.311

AC:

10309

AN:

33178

American (AMR)

AF:

0.0475

AC:

2053

AN:

43262

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

1571

AN:

25842

East Asian (EAS)

AF:

0.0720

AC:

2814

AN:

39062

South Asian (SAS)

AF:

0.0341

AC:

2875

AN:

84208

European-Finnish (FIN)

AF:

0.0282

AC:

1466

AN:

51974

Middle Eastern (MID)

AF:

0.0664

AC:

382

AN:

5752

European-Non Finnish (NFE)

AF:

0.0344

AC:

38026

AN:

1106876

Other (OTH)

AF:

0.0594

AC:

3560

AN:

59924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2837

5674

8510

11347

14184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1656

3312

4968

6624

8280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.115

AC:

17439

AN:

152302

Hom.:

2042

Cov.:

AF XY:

0.113

AC XY:

8436

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.303

AC:

12605

AN:

41546

American (AMR)

AF:

0.0687

AC:

1052

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3470

East Asian (EAS)

AF:

0.0882

AC:

457

AN:

5184

South Asian (SAS)

AF:

0.0393

AC:

190

AN:

4830

European-Finnish (FIN)

AF:

0.0297

AC:

316

AN:

10626

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0347

AC:

2362

AN:

68020

Other (OTH)

AF:

0.102

AC:

215

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

715

1429

2144

2858

3573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0691

Hom.:

702

Bravo

AF:

0.127

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 26, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Methylmalonic acidemia due to transcobalamin receptor defect

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.5

(source)

DANN

Benign

0.80

PhyloP100

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over